Malignant brain tumours are rapidly progressive and resistant to most treatments. In the last eighty years, long-term survival has improved from just six to eighteen months even with state-of-the-art standard of care (surgery, chemotherapy, and radiotherapy). Neurodegenerative disease such as Parkinson's Disease and Alzheimer's Disease also represent unmet clinical needs.
With the promise of new cell based therapies, there is an urgent need for non-invasive, readily available and translatable methods of detecting and quantifying cells in vivo. The development of this imaging technology will enable visualization of biological processes where the fate, localization and long term viability of therapeutic cells can be monitored, which will greatly increase the value of clinical exploration in this area.
By way of example, T-cell therapy, particularly chimeric antigen receptor (CAR) therapy, is an extremely promising cellular therapy that has demonstrated remarkable efficacy in oncological research and clinical practice. Nevertheless, the fate of the therapeutic T cells in clinical studies remains unclear, particularly in central nervous system (CNS) where the engraftment of the T-cells is appreciably more challenging to measure. Despite the continued advancements in monitoring reporter gene expressing T-cells in the peripheral nervous system there is no translatable or clinical standard for tracking cells in the CNS, in particular in the brain.
When assessing CAR T-cell targeting B-cell malignancies, it is possible to sample sites of CAR T-cell activity: i.e. peripheral blood, marrow and even lymph-nodes. This is clearly not possible with CNS disease and information regarding the biodistribution of the therapeutic cells is not provided. In human subjects, MRI and nuclear imaging approaches have been developed to track cellular therapies. These methods typically rely on transient (direct) labelling, for instance, tagging cells with paramagnetic iron oxide particles (for MRI), or with radiotracers (SPECT/PET). However, these transient labelling approaches are not well suited to CAR T-cell tracking as dilution of contrast agent during cell division and/or its radioactive decay confines imaging to a short window after administration, and as such, limits visualisation of the long-term viability of therapeutic cells.
There is thus a need for improved methods of detecting therapeutic cells, for example CAR-expressing cells, in the CNS of a subject.